Poloxamer 188 is a synthetic surfactant that reduces the viscosity of whole blood without hemodilution. It is postulated that poloxamer 188 would improve outcome if administered during retransfusion following hemorrhage. Rabbits were anesthetized and instrumented for 3 h of hemodynamic monitoring. After stabilization, blood was withdrawn over a 5 min period to reduce mean arterial pressure to 35 mmHg (4.7 kPa). Following a 60 min shock period, animals were randomly assigned to 1 of 5 experimental groups (n = 8 in each): [1] SHOCK (no retransfusion); [2] TRANSFUSION (retransfusion of autologous shed blood); [3] VOLUME (retransfusion with autologous blood and infusion of an additional volume of normal saline equivalent to the volume of poloxamer 188 given in the next 2 experimental groups); [4] LOW and [5] HIGH drug (i.v. bolus of 200 mg/kg of poloxamer 188 over 5 min at retransfusion, followed by a continuous infusion of poloxamer 188 at 50 mg/kg/hr in the LOW drug group and 200 mg/kg/hr in the HIGH drug group). All animals in a surgery CONTROL group (n = 6) remained stable during the 3 h monitoring period. In contrast, none of the animals in the SHOCK group remained alive, confirming this to be a relevant model of trauma and severe hemorrhagic shock. There were significantly more animals surviving at the end of the monitoring period in the two groups that received poloxamer 188 (numbers of animals alive after 3 h = 7 of 8 in the HIGH group and 6 of 8 in the LOW group) compared to the TRANSFUSION (4 of 8) and VOLUME (2 of 8) groups. Our results suggest that poloxamer 188 may produce a beneficial short-term effect in a rabbit model of trauma and severe hemorrhagic shock.